crossing96/oncoscreening huggingface dataset:
The impact of grading scheme on non-muscle invasive bladder cancer progression: potential utility of hybrid grading schemes.	Non-muscle invasive bladder cancer (NMIBC) grade is a major determinant of progression risk. The most widely utilised grading systems are the World Health Organization (WHO) 1973 and 2004 schemes. Recent publications suggest the utility of combining both into a four-tier or a hybrid three-tier system, subdividing WHO 2004 high grade into two separate categories while maintaining low grade as a single group. We identified two retrospective cohorts of bladder resections/biopsies of papillary urothelial NMIBC with long term clinical follow-up. The sentinel specimen was assessed for WHO 2004 and 1973 grade, along with pathological stage and carcinoma in situ. Each case was additionally stratified into a hybrid three-tier system (low grade; high grade, grades 2 and 3) and a four-tier system (low grade, grades 1 and 2; high grade, grades 2 and 3). Uni- and multivariable analysis for progression and event free survival (PFS/EFS) were calculated along with the time dependent area under the curve (AUC) for each grading scheme. There were 609 cases (Cohort A, n=343; Cohort B, n=266), including 449 (74%) pTa, 156 pT1 (26%) and four pTx with 338 (56%) low grade (177, grade 1; 161, grade 2) and 271 (44%) high grade (137, grade 2; 134, grade 3). A total of 108 patients progressed (17.7%): 97 high grade, (grade 3, n=59; grade 2, n=38). Multivariable analyses of PFS with the hybrid 3- and 4-tier systems showed higher Harrell's concordance indices (0.851 and 0.853, respectively) than WHO 1973 (0.844) and WHO 2004 (0.846). In both cohorts AUC values were higher (0.77-0.85) for the two hybrid grading systems compared to WHO 1973 or WHO 2004 (0.72-0.82). Similar results were seen on analysis of EFS. The data support the use of a hybrid three-tier or four-tier grading system to improve stratification of NMIBC patients.	bladder
Mutually exclusive mutation profiles define functionally related genes in muscle invasive bladder cancer.	Muscle Invasive bladder cancer is known to have an abundance of mutations, particularly in DNA damage response and chromatin modification genes. The role of these mutations in the development and progression of the disease is not well understood. However, a mutually exclusive mutation pattern between gene pairs could suggest gene mutations of significance. For example, a mutually exclusive mutation pattern could suggest an epistatic relationship where the outcome of a mutation in one gene would have the same outcome as a mutation in a different gene. The significance of a mutually exclusive relationship was determined by establishing a normal distribution of the conditional probabilities for having a mutation in one gene and not the other as well as the reverse relationship for each gene pairing. Then these distributions were used to determine the sigma-magnitude of standard deviation by which the observed value differed from the expected, a value that can also be interpreted as the 'p-value'. This approach led to the identification of mutually exclusive mutation patterns in KDM6A and KMT2D as well as KDM6A and RB1 that suggested the observed mutation pattern did not happen by chance. Upon further investigation of these genes and their interactions, a potential similar outcome was identified that supports the concept of epistasis. Knowledge of these mutational interactions provides a better understanding of the mechanisms underlying muscle invasive bladder cancer development, and may direct therapeutic development exploiting genotoxic chemotherapy and synthetic lethality in these pathways.	bladder
The association between NOTCH3 expression and the clinical outcome in the urothelial bladder cancer patients.	Disrupted NOTCH activity is a driving event in urothelial bladder cancer (UBC). After activation by hypoxia, the NOTCH3 receptor participates in tumor cell proliferation, acquisition of the epithelial-mesenchymal transition phenotype, and angiogenesis. The aim was to analyze the association of NOTCH3 expression with histopathological and clinical parameters, and to determine its predictive impact on the clinical outcome in UBC patients. The present research included 614 UBC samples incorporated in paraffin tissue microarrays, evaluated by immunohistochemistry for NOTCH3 expression. The accrual period was four years, while the follow-up period was two years. The membranous expression was semi-quantified (0-3), and the mean degree was 1.81±0.94. Criteria for semi-quantification the NOTCH3 expression were the intensity of the staining and the percentage of positive cells. The samples with negative (0) and weak (1) NOTCH3 immunohistochemical (IHC) score were considered negative, while the samples that showed moderate (2) and strong (3) expression were considered positive. Higher degree of positivity was associated with higher risk of cancer-specific mortality (p<0.001). Independent predictors for cancer-specific mortality were NOTCH3 expression and high stage (p<0.001). NOTCH3 expression was not a statistically significant predictor of recurrence-free survival (p=0.816). This study indicated that NOTCH3 is a predictor of poor outcome, suggesting that the NOTCH3 could be potentially reliable IHC marker for selecting the UBC patients that would require more intensive follow-up, especially if they diagnosed in higher stage, with divergent differentiation in pathological report, and without recurrences which would lead them to more frequent medical assessments.	bladder
Context-Based Identification of Muscle Invasion Status in Patients With Bladder Cancer Using Natural Language Processing.	PURPOSE: Mortality from bladder cancer (BC) increases exponentially once it invades the muscle, with inherent challenges delineating at the population level. We sought to develop and validate a natural language processing (NLP) model for automatically identifying patients with muscle-invasive bladder cancer (MIBC). METHODS: All patients with a Current Procedural Terminology code for transurethral resection of bladder tumor (TURBT; n = 76,060) were selected from the Department of Veterans Affairs (VA) database. A sample of 600 patients (with 2,337 full-text notes) who had TURBT and confirmed pathology results were selected for NLP model development and validation. The NLP performance was assessed by calculating the sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and overall accuracy at the individual note and patient levels. RESULTS: In the validation cohort, the NLP model had average overall accuracies of 94% and 96% at the note and patient levels. Specifically, the F1 score and overall accuracy for predicting muscle invasion at the patient level were 0.87% and 96%, respectively. The model classified nonmuscle-invasive bladder cancer (NMIBC) with overall accuracies of 90% and 93% at the note and patient levels. When applying the model to 71,200 patients VA-wide, the model classified 13,642 (19%) as having MIBC and 47,595 (66%) as NMIBC and was able to identify invasion status for 96% of patients with TURBT at the population level. Inherent limitations include a relatively small training set, given the size of the VA population. CONCLUSION: This NLP model, with high accuracy, may be a practical tool for efficiently identifying BC invasion status and aid in population-based BC research.	bladder
Prognostic role of ΔNp63 expression in canine transitional cell carcinoma of the urinary bladder.	BACKGROUND: Decreased p63 protein expression in canine transitional cell carcinoma (TCC) of the urinary bladder is associated with vascular invasion of the tumor, metastasis, and shortened survival. ΔNp63, an isoform of p63, is downregulated in high-grade invasive urothelial carcinoma in humans. However, the clinical significance of ΔNp63 expression in canine urinary bladder tumors is unknown. Therefore, it is essential to investigate ΔNp63 expression patterns in TCC, the most common urinary bladder tumor in dogs. AIM: This study aimed to evaluate the expression and role of ΔNp63 in canine TCC of the urinary bladder. METHODS: ΔNp63 expression was compared between the normal canine urinary bladder, polypoid cystitis, and TCC. The correlation of ΔNp63 expression with histopathological and clinical findings were further evaluated, and its usefulness as a prognostic factor was examined. RESULTS: We observed that ΔNp63 was highly expressed in dogs' normal urinary bladder and polypoid cystitis, and its expression levels were low in TCC. Furthermore, low levels of ΔNp63 expression were associated with vascular invasion, metastasis, and shortened survival in dogs with TCC. CONCLUSION: These results indicate that ΔNp63 expression could serve as a valuable biomarker for invasion, metastasis, and prognosis of canine TCC of the urinary bladder.	bladder
Risk of recurrence and long-term mortality following radical cystectomy for bladder cancer.	PURPOSE: To investigate the risk of recurrence and long-term mortality after radical cystectomy (RC) for bladder cancer (BC) at a high-volume tertiary referral center in Denmark over 19 years. MATERIALS AND METHODS: Patients undergoing RC between the 1st of January 2000 to 31st of December 2018 were included. Patient data were manually retrieved from electronic patient files. Follow-up ended 18th of May 2020. Cumulative incidences were used to assess risk of recurrence and mortality using competing risk modelling. Cause-specific Cox regression models were used for multivariable analysis. RESULTS: A total of 1267 patients underwent RC of which 1042 were eligible for analysis. Overall mortality was 40% and 56% after 5 and 10 years, respectively. The cumulative incidence of recurrence and BC specific mortality was high within the first 2 years. Only 3.2% of the patients with recurrence were alive at the end of follow-up. The cumulative incidence of BC mortality after 5 years was 6.7% (95% CI 3.6-9.9) and 10% (95% CI 6.8-14) for patients with ≤ pT1bN0 and pT2N0, respectively. For patients with lymph node positive disease the cumulative incidence of BC mortality after 5 years was 65% (95% CI 58-71). CONCLUSIONS: We found a significant risk of recurrence and disease-specific mortality following RC for BC, especially within the first 2 years following surgery. Our data seem comparable to other large cohorts. The chance of long-term survival following recurrence is low and there is a continuous need to improve adjuvant or salvage strategies following RC.	bladder
Artificial intelligence: A promising frontier in bladder cancer diagnosis and outcome prediction.	Bladder cancer (BCa) is the most common malignancy of the urinary tract and the most expensive malignancy to treat over the patients' lifetime. In recent years a number of studies have utilized Artificial Intelligence (AI) algorithms to perform certain clinical tasks involved in BCa diagnosis and outcome prediction. These tasks include automatic tumor detection, staging, and grading, bladder wall segmentation, as well as prediction of recurrence, response to chemotherapy, and overall survival. Despite the promising results reported, AI algorithms have not been fully integrated into the clinical workflow. In this article we (1) provide an accessible introduction to the fundamental nomenclature and concepts in AI, (2) review the literature to explore how AI is used for BCa diagnosis and outcome prediction, and (3) present our perspective on the obstacles that must be removed before AI algorithms can enter the mainstream of cancer management.	bladder
Adeno-associated virus-delivered alpha synuclein inhibits bladder cancer growth via the p53/p21 signaling pathway.	Alpha-synuclein (α-syn), encoded by the SNCA gene, is a major participant in the pathophysiology of Parkinson's disease (PD). Its functions have been reported to be related to apoptosis induction, the elevation of oxidative stress, mitochondrial homeostasis, cell-cycle aberrations, and DNA-related interactions. Evidence obtained in recent studies suggests a possible link between α-syn and cancer development. Bladder cancer (BCa) is the second most common genitourinary malignancy, with the population of survivors of BCa increasing worldwide. In this study, we show that α-syn expression was significantly downregulated in BCa. In vitro and in vivo experiments showed that α-syn could significantly inhibit BCa cell proliferation by arresting the cell cycle in the S phase via upregulation of p53 expression mediated by DNA damages. Further experiments showed that overexpression of α-syn delivered by adeno-associated viruses (AAVs) exerted inhibitory effects on the growth of BCa tumors. These findings indicate that αα-syn is a functional tumor suppressor that can inhibit the proliferation of BCa cells by activating the p53/p21 signaling pathway. Our present study provides insights into the roles of α-syn in BCa and suggests that α-syn may be a novel therapeutic target for the treatment of BCa.	bladder
The effect of CT high-resolution imaging diagnosis based on deep residual network on the pathology of bladder cancer classification and staging.	BACKGROUND AND OBJECTIVE: To study the high-resolution CT image based on deep residual network to efficiently and accurately predict the staging diagnosis of bladder tumors. METHODS: The image was processed with super-resolution to restore the missing details of the image. The CT data of 75 bladder patients who were treated in our hospital from June to December 2013 were collected. And obtain the patient's classification and staging information through pathology, which is used to establish a model of ResNet structure combined with non-Local attention mechanism. The clinical data of 76 patients with bladder disease admitted to our hospital from May 2018 to August 2021 were randomly selected, and the imaging and accuracy of CT diagnosis were retrospectively analyzed. RESULTS: 52 cases were diagnosed <T1 stage, 16 cases belonged to T2 stage, 2 cases T3 stage, and 2 cases T4 stage. The sensitivity rate of experimental diagnosis was 94.74%, which was not significantly different from the sensitivity rate of preoperative pathological diagnosis. CONCLUSION: CT based on deep residual network has high application value in the diagnosis and staging of bladder cancer, can effectively improve the diagnostic accuracy, and is worthy of clinical application.	bladder
Neoadjuvant versus adjuvant chemotherapy in bladder cancer: a nationwide cohort study.	PURPOSE: Radical cystectomy is the standard of care for muscle-invasive bladder cancer. However, the 5-year survival rate is only about 50%. Therefore, additional treatments are needed. We compared the perioperative outcomes, overall survival, and treatment trends in patients with bladder cancer who underwent radical cystectomy and either neoadjuvant or adjuvant chemotherapy using nationwide population-based data. MATERIALS AND METHODS: We collected the data of patients diagnosed with bladder cancer treated with radical cystectomy between 2004 and 2016 using the National Health Insurance Service database. We evaluated overall treatment trends. The neoadjuvant chemotherapy and adjuvant chemotherapy groups were matched by propensity score. Cox proportional hazard analysis and Kaplan-Meier analysis were used to assess survival. RESULTS: Of 6134 patients, 1379 underwent adjuvant chemotherapy and 389 underwent neoadjuvant chemotherapy. The utilization rate of neoadjuvant chemotherapy increased from 6.4 to 12.2% from 2004 to 2016 (p = 0.018). The administration rate and number of granulocyte colony-stimulating factor cycles were lower in the neoadjuvant chemotherapy group than in the adjuvant chemotherapy group (p < 0.001 and p = 0.027, respectively). After propensity score matching, the neoadjuvant chemotherapy group had significantly better overall survival than the adjuvant chemotherapy group (p = 0.004). In multivariate analysis, neoadjuvant chemotherapy was associated with better overall survival (hazard ratio 0.77, 95% confidence interval 0.65-0.92, p = 0.003). CONCLUSIONS: Neoadjuvant chemotherapy was associated with lower granulocyte colony-stimulating factor administration and better overall survival than adjuvant chemotherapy. Neoadjuvant chemotherapy should be considered for patients with bladder cancer who undergo radical cystectomy.	bladder
En Bloc Resection for Bladder Tumors: An Updated Systematic Review and Meta-Analysis of Its Differential Effect on Safety, Recurrence and Histopathology.	PURPOSE: En bloc resection for bladder tumors has been developed to overcome shortcomings of conventional transurethral resection of bladder tumors with regard to safety, pathological evaluation and oncologic outcomes. However, the potential benefits and utility compared to conventional transurethral resection of bladder tumors have not been conclusively demonstrated. We aimed to update the current evidence with focus on the pathological benefits of en bloc resection for nonmuscle-invasive bladder cancer. MATERIALS AND METHODS: The PubMed®, Web of Science™ and Scopus® databases were searched in August 2021 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they compared safety, and pathological and clinical outcomes in patients who underwent en bloc resection with conventional transurethral resection of bladder tumors. RESULTS: Overall, 29 studies comprising 4,484 patients were eligible for this meta-analysis. Among 13 randomized controlled trials, the pooled 12- and 24-month recurrence risk ratios were not statistically different between the 2 surgical techniques (0.96, 95% CI 0.74-1.23 and 0.83, 95% CI 0.55-1.23, respectively). The pooled risk ratio for bladder perforation was 0.13 (95% CI 0.05-0.34) in favor of en bloc resection. In randomized controlled trials, the differential rates of detrusor muscle presence (pooled RR 1.31, 95% CI 1.19-1.43) and of detectable muscularis mucosae (pooled RR 2.69, 95% CI 1.81-3.97) were more likely in patients receiving en bloc resection. Patients who underwent en bloc resection had a lower rate of residual tumor at repeat transurethral resection than those treated with conventional transurethral resection of bladder tumors in 1 randomized controlled trial and 3 observational studies (pooled RR 0.47, 95% CI 0.31-0.71). CONCLUSIONS: En bloc resection for bladder tumors seems to be safer, and to yield superior histopathological information and performance compared to conventional transurethral resection of bladder tumors. Despite the failure to improve the recurrence rate, the more accurate histopathological analysis is likely to improve clinical decision making and care delivery in nonmuscle-invasive bladder cancer.	bladder
Downregulation of m(6) A writer complex member METTL14 in bladder urothelial carcinoma suppresses tumor aggressiveness.	N6-methyladenosine (m(6) A) and its regulatory proteins have been associated with tumorigenesis in several cancer types. However, knowledge on the mechanistic network related to m(6) A in bladder cancer (BlCa) is rather limited, requiring further investigation of its functional role. We aimed to uncover the biological role of m(6) A and related proteins in BlCa and understand how this influences tumor aggressiveness. N6-adenosine-methyltransferase catalytic subunit (METTL3), N6-adenosine-methyltransferase noncatalytic subunit (METTL14), protein virilizer homolog (VIRMA), and RNA demethylase ALKBH5 (ALKBH5) had significantly lower expression levels in BlCa compared to that in normal urothelium. METTL14 knockdown led to disruption of the remaining methyltransferase complex and a decrease in m(6) A abundance, as well as overall reduced tumor aggressiveness (decreased cell invasion and migration capacity and increased apoptosis). Furthermore, in vivo, METTL14 knockdown caused tumor size reduction. Collectively, we propose methyltransferase METTL14 as a key component for m(6) A RNA deposit and that it is closely related to BlCa progression, playing an important role in tumor aggressiveness. These data contribute to a better understanding of the m(6) A writer complex, which might constitute an appealing therapeutic target.	bladder
[A PRIMARY BLADDER ALVEOLAR SOFT PART SARCOMA: A CASE REPORT].	A 32-year-old woman was admitted to our department for hematuria and dysuria.Computed tomography (CT) and cystoscopy revealed a 2-cm pedunculated tumor with rich blood supply and a smooth surface in the bladder trigone. We performed a transurethral resection of bladder tumor. The pathologic diagnosis was alveolar soft part sarcoma (ASPS). CT, bone scintigraphy, positron emission tomography, and pelvic magnetic resonance imaging revealed no other lesions; thus, she was diagnosed as having a primary bladder ASPS. Postoperative follow-up with regular cystoscopies and CTs over 10 years have shown no local recurrence or metastasis.Primary ASPS of the bladder is exceedingly rare, and this case is the 8th case (the 2nd case in Japan) reported in literature.	bladder
Residual CIS after neoadjuvant chemotherapy and radical cystectomy for muscle invasive bladder cancer: Implications for neoadjuvant trials.	PURPOSE: To better define surrogate endpoints for neoadjuvant chemotherapy (NAC) trials in patients with muscle-invasive bladder cancer. We compared survival in patients with carcinoma in-situ (CIS) only vs. complete response following NAC and radical cystectomy (RC). MATERIALS AND METHODS: Patients with cT2-4N0M0 disease treated with NAC and RC between 2001 and 2018 were stratified by response: complete response (CR, pT0N0), partial response (PR, pTaN0, pT1N0+/-CIS), CIS-only (pTisN0), stable disease (SD, pT2N0), or progressive disease (PD, >pT2N0). Primary endpoints were overall survival (OS) and risk of recurrence in patients with CIS-only vs. CR. Multivariable Cox proportional hazards regression model was used for OS and a competing risks proportional hazards model was used for risk of recurrence. RESULTS: Of 1,406 patients in our institution cohort, 340 patients met inclusion criteria. Kaplan-Meier mean estimates of OS for CR and CIS-only were 108.9 months (95% CI 89.7-127.9) and 125.8 months (95% CI 112.3-139.3), respectively (P = 0.13). Cox proportional hazards model found no difference in OS between patients with PR (HR 1.06, 95% CI 0.33-2.58, P = 0.897) or CIS-only (HR 0.422, 95% CI 0.15-1.18, P = 0.101) when compared to CR. The risk of recurrence was similar between patients with CIS-only (HR 0.73, 95% 0.29-1.84, P = 0.49) and PR (HR 1.32, 95% CI 0.54-3.29, P = 0.54) when compared to CR on competing risks analysis. CONCLUSIONS: Residual CIS-only after NAC and RC demonstrated similar survival outcomes when compared to patients with pathologic CR. Further study in large multi-institutional cohorts may further validate CIS-only as an additional surrogate endpoint after NAC and may inform future trials.	bladder